Olokizumab Improves Patient-Reported Outcomes in Patients with Active Rheumatoid Arthritis up to 106 Weeks (Results from the Open-Label Extension of Phase III Randomized Clinical Trials)

INTRODUCTION: This analysis evaluated the effects of olokizumab (OKZ) on patient-reported outcomes (PROs) after up to 106 weeks of treatment in patients with active rheumatoid arthritis (RA) refractory to methotrexate (MTX; MTX-inadequate response [MTX-IR]) or refractory to tumor necrosis factor inhibitor (TNFi; TNFi-inadequate response [TNFi-IR]). METHODS: Post-hoc analysis was performed of pooled PROs from phase III, double-blind, placebo-controlled trials (CREDO1/2 MTX-IR; CREDO3 TNFi-IR; NCT02760368/ NCT02760407/NCT03225932) and their open-label extension (OLE; up to 106 weeks) in adults with active RA despite treatment with MTX or TNFi. Patients were treated with OKZ 64 mg every 2 weeks (q2w) or every 4 weeks (q4w) + MTX versus MTX + placebo (weeks 0-24) or active comparator (CREDO2), followed by an OLE (all OKZ). The PROs analyzed were patient global assessment; pain (visual analog scale); Health Assessment Questionnaire Disability Index (HAQ-DI); 36-Item Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (FACIT-F); Work Productivity Survey Rheumatoid Arthritis (WPS-RA) and the European Quality of Life-Five-Dimension Questionnaire (EQ-5D). Changes from baseline at weeks 12, 24 and 106 were analyzed using a mixed model for repeated measures; analyses included percentages of patients reporting improvements ≥ minimal clinically important difference (MCID). RESULTS: By week 12, treatment with OKZ compared to placebo (PBO) resulted in greater numerical and clinically meaningfully changes from baseline in all PROs for patients refractory to MTX: the HAQ-DI was - 0.60 for OKZ q2w, - 0.58 for OKZ q4w and - 0.34 for PBO; pain VAS was - 33.26, - 32.51, - 18.39, respectively; and the FACIT-F was 8.47, 8.42 and 4.69, respectively (p < 0.0001). Similar but less prominent improvements were noted in the patients with TNFi-IR. Post hoc analyses demonstrated a higher proportion of patients receiving OKZ reported improvements ≥ MCID versus those receiving PBO (p < 0.05) in all PROs in both groups at week 12. For patients treated with OKZ, the observed improvements from baseline were maintained and increased in magnitude through week 106. CONCLUSION: Treatment with OKZ over 106 weeks resulted in sustained numerically greater and clinically meaningful improvements in PROs compared to baseline in both RA patients with MTX-IR and those with TNFi-IR. These findings support the long-term benefit of OKZ on PROs. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02760368, NCT02760407, NCT02760433, NCT03120949.